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Flashcards in Animal Models Deck (16)
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Classical models of Parkinson's

Toxic models:
- MPTP (mice, primates)
- 6-hydroxydopamine (rats, mice)
- paraquat (rats, mice)
- rotenone (rats)


PD sporadic vs familial

90% - sporadic
- environment
- possibly genetic factors
10% - familial
- mutations


Symptoms of PD

Postural imbalance
Olfactory loss
Cognitive disorders (implicit memory)
Affective disorders (depression / anxiety / apathy)
Sleep disturbances
Autonomic disorders (hypotension)
Digestive symptoms (constipation)

Other Symptoms:
- Constipation (Lewy bodies found in the neurons of the intestinal wall)
- Various neurons with long axons show Lewy bodies before the dopaminergic ones
- Sleep disorders
- Depression
- psychosis
- Anosmia

- Mask face
- Micrographia
- Hypersalivation


Allocation concealment

Concealing the allocation sequence from those assigning animals to intervention groups, until the moment of assignment.



Systematic distortion of the estimated intervention effect away from the “truth,” caused by inadequacies in the design, conduct, or analysis of an experiment.


Blinding (masking)

Keeping the persons who perform the experiment, collect data, and assess outcome unaware of the treatment allocation


External validity

The extent to which the results of an animal experiment provide a correct basis for generalisations to the human condition.


Intention-to-treat analysis

Analysis of data of all animals included in the group to which they were assigned, regardless of whether they completed the intervention.


Internal validity

The extent to which the design and conduct of the trial eliminate the possibility of bias.


Biases threatening internal validity:

- selection bias (biased allocation to treatment groups) [sol.: randomization, allocation concealment]
- performance bias (systematic differences in care between groups apart from the intervention) [sol.: blinding]
- detection (ascertainment, assessment, or observer bias: systematic distortion of the results of a study that occurs when the person assessing the outcome has knowledge of treatment assignment) [sol.; blinding]
- attrition bias (unequal occurrence and handling of deviations from protocols and loss to follow-up between treatment groups) [sol:blinding, intention-to-treat, reporting drop outs]
- false positive report bias (bias due to poor statistical power) [sol: adequate sample size]


Common problems with external validity:

- Induction of one disease in animals that are young and healthy, whereas in patients the disease mainly occurs in elderly people with co-morbidities.
- Assessment of the effect of a treatment in a homogeneous group of animals versus a heterogeneous group of patients.
- The use of either male or female animals, whereas the disease occurs in male and female patients.
- use of models for inducing a disease or injury with insufficient similarity to the human condition.
- Unrealistic timing and dosage of treatment in animals vs human.
- Differences in outcome measures and the timing of outcome assessment between animal studies and clinical trials.


Aspects of a study to be reported:

- sample size calculation
- eligibility criteria
- treatment allocation (If this allocation was by randomisation, the method of randomisation)
- allocation concealment
- blinding
- flow of animals (Flow of animals through each stage of the study, with a specific attention to animals excluded from the analyses. Reasons for exclusion from the analyses.)
- control of physiological variables
- control of study conduct (Whether a third party controlled which parts of the conduct of the study.)
- statistical


Stages for describing seizure behavior:

Racine 1972
- I freeze / mild facial clonus
- II severe facial clonus
- III forelimb clonus
- IV rearing
- V falling
Fully Kindled = 5 * stage V


EEG readout info in epilepsy

- latency - time between hit and
- epileptic spikes
- seizure duration
- spike frequency


Side effects of VNS:

- bradycardia and decreased respiration rate (at stronger current)
- SO2 96% to 86%
- coughing
- immobility
- Horner’s syndrome
- vocalizing
- polyuria
- trears
- headturn
- >defecation frequency
- drooling swallow


Features of VNS that define its efficiency

- electrode design, ?
- electrode is (not) around the carotid artery, ?
- stimulation parameters
- anesthesia no/yes, how?
- responder definition